Renal toxicity and gouty arthritis are two of the multiple results of lead poisoning. In addition, lead causes degradation of nucleic acids and a study of the effects of lead on the enzymes of purine metabolism has been started in order to correlate the clinical observations with biochemical events. These preliminary studies showed that the enzyme, guanine aminohydrolase (guanase), was inhibited by Pb2 ion at 10 to the minus 7th power M. The role of guanase is to convert guanine to xanthine. Since guanine is very insoluble, lead poisoning might lead to accumulation of guanine precipitates in vivo. Indeed, elevated levels of guanine have been found in lead-poisoned rabbits. These preliminary studies have shown that Hg2 ion and Ag ion, but not Cd2 ion or any other metal tested, was inhibitory to guanase. This proposal, therefore, is to study the effects of these heavy metal pollutants at low levels (sub clinical) and at high levels characteristic of acute poisoning in vitro on the enzyme and in vivo on the metabolism of guanine. The study would also include administration of C14 guanine to poisoned and normal animals to determine in which organs free guanine accumulates. Another goal of this proposal will be to examine the deposits (accumulated in the joints) of patients with saturnine and normal gout in order to determine if guanine is present in the precipitates. Lead and mercury are volatile components of coal, and lead is an atmospheric contaminant due to its continued use in gasoline. Mercury is also a water contaminant. Therefore, this study would give an indication of the extent ot which these pollutants give rise to renal and metabolic problems related to the accumulation of the highly insoluble metabolite guanine.